Human Chorionic Gonadotrophin And Weight Loss

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SAMTadults with peptic ulcers. 1 This could be due to the fact thatnot all patients underwent regular follow-up endoscopy .afterapparent healing. In adults it is now well known that manyrelapses are entirely asymptomatic and it is possible that thesame applies in children. After initial diagnosis and treatment,no patient subsequently presented with complications ofgastro-intestinal bleeding or perforation. It would seem thatthe consequences of missing an asymptomatic relapse in childhood are rarely serious.In conclusion, although relatively infrequent, peptic ulcersin childhood are probably more common than generally realised. Diagnosis of the condition presents a challenge anddemands a high level of awareness if diagnostic delays are tobe avoided. Despite a high index of suspicion some childrenwill present for the ftrst time with features related to intestinalblood loss without preceding symptoms. Earlier diagnosis inthese will remain impOssible. In children with abdominal painthe diagnosis must always be considered' and probably themost valuab.le clinical clues are localised epigastric tendernessand anaemia. Failure to consider this possibility in childrenpresenting with abdominal pain may lead to a considerableVOL 7717 FEB 1990185delay in reaching the correct diagnosis. The conftrmatorydiagnostic investigation of choice is upper gastro-intestinaltract endoscopy. Where this is not available a barium mealexamination remains an alternative but false-negative studiesoccur in a signiftcant number of cases in childhood. 6REFERENCESJ Gaslroemerol 1980;73: 75-80.Murphy MS, Eastham EJ, Jimenez N, Nelson R, Jackson RH. Duodenalulceration: review of 110 cases. Arch Dis Child 1987; 62: 554-558.Robb JDA, Thomas PS, Orszulok J, Odling-Smee GW. Duodenal ulcer inchildren. Arch Dis Child 1972; 47: 688-696.Habbick BF, Meirose AG, Grant Je. Duodenal ulcer in childhood. Arch VisChild 1968; 43: 23-27.Seagram CGF, Stephens CA, Cumming WA. Peptic ulceration at theHospital for Sick Children, Toronto, during the 20-year period 1949 - 1969.J Ped,alr Surg 1973; 8: 407-413.Nord KS. Peptic ulcer disease in the pediatric population. Pedialr ClinNorlhAm 1988; 35: 117-140.Marks IN, Girdwood AH. Recurrence of duodenal ulceration in patients onmaintenance sucralfate: a 12-month follow-up study. S Afr Med J 1985; 67:626-628.I. Nord KS, Lebenthal E. Peptic ulcer in children. Am2.3.4.5.6.7.Human chorionic gonadotrophin and weight lossA double-blind, placebo-controlled trialB. BOSCH,I. VENTER,R. I. STEWART, S. R. BERTRAMSummaryLow-dose human chorionic gonadotrophin (HCG) combinedwith a severe diet remains a popular treatment for obesity,despite equivocal evidence of its effectiveness. In a doubleblind, placebo-controlled study, the effects of HCG on weightloss were compared with placebo injections. Forty obesewomen (body mass index 30 kg/m 2) were placed on thesame diet supplying 5000 kJ per day and received dailyintramuscular injections of saline or HCG, 6 days a week for 6weeks. A psychological profile, hunger level, body circumferences, a fasting blood sample and food records wereobtained at the start and end of the study, while body weightwas measured weekly. Subjects receiving HCG injectionsshowed no advantages over those on placebo in respect ofany of the variables recorded. Furthermore, weight ·Ioss onour diet was similar to that on severely restricted intake. Weconclude that there is no rationale for the use of HCGinjections in the treatment of obesity.S Atr Med J 1990; 77: 185-189.Department of Medical Physiology and Biochemistry,University of Stellenbosch, Parowvallei, CPB. BOSCH, RSC HONS, M.SC (MED.), M.B. CH.RR. I. STEWART, M.R CH.B., PH.D., F.CCP.S. R. BERTRAM, M.SC(MED.)Department of Dietetics, Tygerberg Hospital, Parowvallei,CPI. VENTER, RSC. (DIET.) HONSAccepted 14 Mar 1989.Reprint requests to: Ms S. R. Benram, Dept of Medical Physiology and Biochemistry,Univeniry of Stellenbosch, PO Box 63, Tygerbetg, 1505 RSA.Obesity is a common disorder with a strong association withhean disease, diabetes mellirus, gallbladder disease and pulmonary disorders.1-5 In many societies it is also associated with adesire to be thin, and many obese individuals are desperate foran effective method of weight loss and weight maintenance.Of the many forms of treatment currently available, the useof low-dose injections of human chorionic gonadotrophin(HCG) combined with a severe diet has been popular since1954. 6 However, only two srudies have obtained conclusiveevidence that HCG is effective in the treatment of obesityYIn contrast, it has been reported that placebo injections areas effective as HCG in the treatment of obesity.9,lo Despite theequivocal evidence relating to the effectiveness of the regimen,the use of HCG in the treatment of obesity remains popular.A further reservation for the use of HCG is .he use of a verylow-kilojoule diet (2100 kJ) as proposed by Simeons,6 whichcould produce cardiac and metabolic problems I I and is notsuitable for long-term maintenance treatment.Simeons 7 and Gusman 8 claimed that HCG promotes patientcompliance, decreases appetite, facilitates sustained weightloss, causes differential weight loss from waist and hips, andreleases free fatty acids from depot fat, Gusman 8 also reportedthat HCG injections caused no adverse side-effects. Stein etal.,12 however, reported that one previously infertile patientbecame pregnant while receiving a course of low-dose HCGinjections. He advised warning all patients receiving HCG forweight loss to take adequate precautions to prevent pregnancy,even if they had previously been infertile.The purpose of this study was to test the validity of thepurported additional benefits of HCG in the treatment ofobesity, using a 'prudent diet' of 5000 kJ per day instead ofthe usual very-low-kilojoule diets.

186SAMJVOL 7717 FEB 1990Subjects and methodsEthical approval was obtained to conduct a double-blind,placebo-controlled trial on forty obese white women (bodymass index (BMI) 30 kg/m 2) randomly selected fromvolunteers responding to an advenisement in a local newspaper. Subjects were advised that they would be randomlyassigned to one of two groups of 20, and that they would onlybe informed of what injections they had received on conclusionof the study. One· group received injections of HCG 125 IU in0,2 ml diluent, in accordance with the recommended dosage,12,13wliile the control group received .injections of 0,2 ml saline(placebo). Subjects were all in good health, as determined by amedical history and examination before commencing the study.One subject had previously been treated with HCG, morethan 1 year before this study.The drugs were prepared separately and dispensed in adouble-blind manner utilising a subject code number that wasonly broken on completion of the course. Fresh HCG solutionwas prepared every 3 days and the solution was stored at 4 Cat all times; individual HCG and saline injections were prepared daily from their respective vials. Intramuscular injectionsinto the lateral upper arm were given at the same time eachday, 6 days a week for 6 weeks. They were given bya projectleader in order to ensure administration of the treatment. Tobe included in the results, patients had to have received aminimum of 34 of the 36 injections.Side-effects·of the drugs were reported and recorded daily.On completion of the programme, subjects were required toquantitate their experience of pain, both during and afteradministration of the injections, on a digital scale of 1 - 5 Cl no pain; 5 very painful).All subjects were placed on the same balanced diet supplying5000 kJ per day. Compliance with the diet was assessed usingdetailed daily food intake records completed by the subjectsfor the 2 weeks before commencement of the course, the fIrst 2weeks of the course and the fInal 2 weeks. For each 2-weekperiod, 3 days (2 weekdays and 1 weekend day) were randomlyselected; the average daily energy intake was then calculatedand taken to represent the average intake over the 2-weekperiod.Once a week, all subjects attended a lecture on topics suchas the causes and treatment of obesity and behavioural changesassociated with obesity and its treatment. Subjects wereweighed before this weekly lecture.For the assessment of serum lipid proflles, venous bloodsamples were drawn after a l2-hour fast at the stan and oncompletion of the course. Body circumferences were measuredat the stan and end of the course by the same examiner usingstandard measuring sites and techniques. 14 Using abdomen,thigh and calf circumferences, body fat percentage was thencalculated according to the method of Katch and McArdle. 14Subjects also completed a psychological questionnaire specifIcally designed to assess psychological status, including moodand self-image. Variables were measured on a graded scale of 1(never) to 5 (always); the lower the score, the more positive thepsychological status. Subjects were also requested to marktheir hunger level on a continuum ranging from 'all the time'through 'sometimes' to 'never'; the level of hunger wasinverSely related to the recorded score.The Wilcoxon matched-pairs signed rank test was used forcomparisons within groups (intragroup), while the MannWhi ey V-test was used for intergroup comparisons.ResultsOf the original 40 participants, 7 (4 from the saline group and3 from the HCG group) did not meet the minimum require-ments for the course. Only the results for the panicipants whosuccessfully completed the course (16 in the saline group and17 in the HCG group) are reponed. Values are expressed asmean standard error of the mean.Average daily energy intakeFig. 1 illustrates the average daily energy intake for the twogroups for the 2 weeks before the study, the fIrst 2 weeks andthe fInal 2 weeks. During the fIrst 2 weeks energy intake wassignilicantly reduced (44,6 5,5% and 44,1 5,5% for thesaline and HCG groups respectively) (P 0,001). Thisdecrease in daily energy intake was maintained for the 6-weekperiod, although there was a slight increase in the energyintake of both groups in the last 2 weeks (12,9 9,2% and 29,4 7,3% for the saline and HCG groups respectively). Althoughthis increase was signilicant in the HCG group only (P 0,05), the differences between the two groups were not signilicant at any stage during the study.12Average Daily Intake (MJ/day)BeforeStart SalineFig. 1. Daily energy intake (meanintake records (see 'Methods').EndHCG SE) was calculated from food.Body mass, BM! and body fatThe initial, fmal and percentage changes in body mass, BMIand body fat for the two groups are shown in Table I. Allvalues were signifIcantly lower (P 0,001) at the conclusion ofthe study.Fig. 2 illustrates average weekly body mass for both groupsover the 6-week study period. There were no differencesbetween the groups in body mass, BMI or percentage body fatat any stage of the trial.105Mass (kg)100959085 '---- ----1---1---- ----1---- ---- o42358Weeks-Fig. 2. Body mass (meanSalineHCG SE) recorded weekly.

SAMT VOL 77 17 FEB 1990187TABLE I. BODY MASS, BMI AND BODY FAT MEASUREMENTSStartBody mass (kg)SalineHCGBMI (kg/m)SalineHCGBody fat (%)SalineHCG96,096,034,7935,47 2,7 2,6 1,09 0,7740,3 1,341,S 1,3EndDecrease (%)91,4 2,7*92,8 2,7*4,9 0,63,4 0,733,1334,28 1,12* 0,82*37,0 1,7*38,3 1,3*4,9 0,63,4 0,78,4 2,17,5 1,5Final values significantly different from the start'p 0,001.Body circumferencesAll body circumferences decreased significantly over thetrial period in both groups, the most significant reductionsoccurring in the trunk and thigh regions. There were nosignificant differences between the groups at any stage of thestudy, and specifically there was no significant additionalreduction of either waist or hip circumferences as a result ofHCG administration (Table II).Lipid profileSerum lipid concentrations are summarised in Table Ill.Only blood cholesterol levels were significantly reduced inboth groups, decreasing from slightly above the normal reference range (3,8 - 5,7 mmoVl) to within the upper limitsthereof. Although the initial high-density lipoprotein (HDL)/total cholesterol ratio was significantly higher (P 0,05) in theHCG group, the percentage changes in this ratio and in theHDL/low-density lipoprotein (LDL) cholesterol ratio werenot significantly different between the groups. The meanHDL/total cholesterol ratios for both groups of women wereunchanged and remained normal ( 0,20) throughout thestudy.Although blood triglyceride concentrations tended todecrease in all subjects over the 6-week period, changes werenot significantly reduced and values remained within theupper limits of the normal range (0,97 - 1,97 mmol/l).Fasting triglyceride and uric acid levels were similar in bothgroups, and remained unchanged for the duration of thestudy.Psychological profileThe psychological questionnaire measured mood and selfimage on a scale of 1 (never) to 5 (always), and the lower theTABLE 11. BODY CIRCUMFERENCES (cm)NeckSalineHCGShoulderSalineHCG. neHCGThighSalineHCGCalfSalineHCGStartEndDecrease (%)36,7 0,436,9 0,536,2 0,4*36,0 0,4**1,3 0,32,3 0,6117,0 1,3117,8 1,6115,0 1,4*116,2 1,5*1,7 0,51,4 0,437,3 0,537,7 1,036,4 0,5*36,7 0,9*2,3 0,62,4 0,5116,3 2,1114,6 2,1112,9 2,1**112,6 2,2**3,0 0,41,7 0,5104,0 2,6103,5 2,799,8 2,8**99,0 2,5**4,2 0,74,3 0,8121,5 2,5122,9 1,7116,9 2,6**119,6 1,7**3,8 0,52,7 0,469,1 0,871,8 1,166,5 1,0**69,S 1,2**3,8 0,53,1 0,541,4 0,741,2 0,640,8 0,7*40,6 0,6*1,3 0,41,3 0,3Final values significantly different from the start'p 0,05."P O,OO1.

188SAMJ VOL 77 17 FEB 1990TABLE Ill. LIPID PROFILETotal cholesterol (mmolll)SalineHCGHDLltotal cholesterolSalineHCGHDL/LDL cholesterolSalineHCGTriglycerides (mmolll)SalineHCGUric acid (mmolll)SalineHCGStartEnd6,22 0,285,81 0,275,79 0,27*5,27 0,26*-7,50- 8,880,24 0,010,30 0,02t0,24 0,010,29 0,02 0,46 3,26 0,03 0,060,39 0,030,50 0,04- 1,15 4,05- 6,00 4,021,84 0,231,58 0,231,52 0,201,39 0,19- 15,63 6,35-7,95 6,670,29 0,020,30 0,010,29 0,020,32 0,02 3,11 2,78 3,36 2,720,400,55Decrease (%)- 2,77 2,64 2,02 2,92Final values significantly different from the start·P O.Ol.Significant inter-group difference:t P 0.05.TABLE IV. PSYCHOLOGICAL PROFILEMoodSalineHCGSelf-imageSalineHCGHunger levelSalineHCGStartEndImprovement (%)18,6 1,119,4 1,017,2 1,517,9 1,4*4,8 8,19,6 3,422,6 1,320,6 1,220,4 1,418,1 1,8*9,2 4,415,1 4,33,7 0,63,9 0,55,8 0,4*6,5 0,5**133,0 43,7225,6 84,0Final values significantly different from the start'P 0.05.··P O,Ol.score the more elevated was the mood and the more positivethe self-image. Although mood was elevated and self-imagewas more positive (P 0,05) at the end of the study in theHCG group only, there were no significant differences betweenthe two groups with respect to percentage change (Table IV).Hunger, on-the' other hand;"was'measured on a scale of 1(always) to 10 (never), with the result that the recorded scorewas inversely related to the level of hunger. On conclusion ofthe study, the perception of hunger was significantly andequally reduced in both groups.Side-effectsNo major side-effects were reported on daily questioning orin response to a written questionnaire on completion of thecourse. Minor side effects reported included headaches (saline1, HCG 2), insomnia (saline 1), pruritus (saline 1) and temporary nocturia (HCG 1). These side-effects were present forless than 3 days and only occurred during the first week. Noneof the subjects developed infections at the injection sites at anystage of the course or in the 2 weeks after the study.There was no difference in the pain experienced by the twogroups. On a scale of 1 (no pain) to 5 (extreme pain), theperceived pain levels were 1,63 0,81 and 1,94 1,24 for thesaline and HCG groups respectively.DiscussionThe major finding of this study was that HCG was no betterthan placebo (saline) in promoting weight loss. Furthermore,none of the claimed additional benefits, namely increasedcompliance, decreased appetite and differential weight lossfrom the hips and thighs, could be substantiated.Critique of th.e studyIn this study, a diet supplying 5000 kJ per day was usedinstead of the very-Iow-energy diets of 2 100 kJ per day6-S,13originally proposed by Simeons in 1954. 6 It has recently beenshown that very-Iow-energy diets lower the resting metabolicrate,15 thus making weight loss more difficult. Furthermore, aprudent diet supplying 5000 kJ per day was selected becausewe have previously shown16 that it produces an average weeklyweight loss of 0,5 - 1,0 kg but is not associated with thecardiac and metabolic abnormalities that can occur with verylow-energy diets. l1 An additional benefit was that it was abalanced diet that subjects could safely continue on completionof the course.In spite of the higher energy equivalent of our diet, averageweight loss over 6 weeks, both for the saline group (5,0 0,5kg) and for the HCG group (4,1 0,6 kg), compares favourably

SAMT VOL 77with weight loss reported by previous workers over a similarperiod of time. Craig et al. 13 reported a total average weightloss of 2,9 kg (HCG) and 4,0 kg (saline) using a modifiedSimeons diet (2300 kJ per day), while Frank l7 reported weightloss of 5,6 kg (HCG) and 5,1 kg (saline) for subjects on a dietsupplying 4300 kJ per day. It would seem therefore that thereis no particular advantage in prescribing very-low-energy diets.Furthermore, when the average weight loss in the presentstudy is compared with the loss reported l6 on this diet alone(7,0 1,8 kg), on the diet combined with an exercise programme (7,0 1,9 kg), or on the diet combined with lecturetherapy (6,3 0,9 kg), it is seen that the injections, whether ofplacebo or HCG, had no added effect on weight loss.Thirty-three of the initial 40 subjects completed the courseof injections despite the inconvenience of daily attendance forthis administration. Three subjects had to withdraw owing tocircumstances beyond their control, but the other 4 subjectsabsconded. This drop-out rate is similar to those recorded byCraig et al. l3 and Stein et al.,J2 but it is significantly lowerthan the 35 out of 66 recorded ·by Frank,17 in whose studyinjections were administered every other day as opposed todaily. On first examination, it does not appear that dailycontact with project leaders has an added advantage withrespect to weight loss. However, if it is assumed that subjectswho absconded did not lose weight, the average weight loss inthe Frank investigation would be significantly lower than inthe studies where subjects received injections daily. Thus itwould appear that daily contact promotes compliance andadherence to the regimen.Analysis of the resultsThe various claims made that HCG assists in weight loss bypromoting patient compliance, decreasing appetite and causingdifferential weight loss from the waist and hips could not besubstantiated by our fmdings.Firstly, patient compliance with the diet, as measured byrecorded food intake, was good throughout the course in boththe placebo and the HCG groups, and no advantages of theHCG could be established. In fact, although there were nosignificant intergroup differences, intake increased significantlyin the HCG group over the last 2 weeks of the study.However, average daily values remained significantly lowerthan those recorded before commencement of the study.Although the improvement in mood and self-image wasstatistically significant only in the HCG group, the percentagechanges of the two groups were not different. The elevatedmood and more positive self-image may be ascribed to theconsistent weight losses experienced by these volunteers.Furthermore appetite, as indicated by the level of hunger, was.significantly reduced in both groups, in spite of the largereduction in average daily kilojoule intake. Simeons' claim6that dietary compliance was assisted by HCG injections as aresult of reduced hunger and a more positive mood couldtherefore also not be substantiated in this study.17 FEB 1990189No supportive evidence was found for the claim that HCGenhances differential weight loss from the waist and hips asreflected by body circumference measurements. The fact thatthere were no intergroup differences in fasting triglyceridelevels mitigates against the claim that this alleged differentialweight loss is mediated by an enhanced depot fat mobilisation.Minimal pain from the injections was experienced by bothgroups, thus concurring with Gusman8 that, despite the manyinjections administered ( 1500), there were no major sideeffects or infections.ConclusionsNone of the claims made in support of HCG as an aid toweight loss could be substantiated in this study. Therefore, theonly reason for giving injections would be to motivate thepatient through daily contact with the administrator, andthrough regular dietary follow-up. However, since the administration of injections combined with diet provided similar, ifnot identical, effects to combination of a 5000 kJ diet withweekly lectures,16 the use of daily injections in itself does notappear to contribute to weight loss. We therefore concludethat there is no rationale for using this particular form oftherapy in the treatment of obesity.REFERENCESI. US Department of Health, Education and Welfare. Reporr of rhe HypercensionTask Force (NIH Publication No. 79-1631). Washington, DC: DHEW,1979: 59-77.2. Drenick EJ. Definition and health consequences of morbid obesity. SurgClin NOTrh Am 1979; 59: 963-975.3. Bray GA. Obesity: definition, diagnosis, and disadvantages. Med J Awr1985; 142: suppl, S2-S8.4. Luce JM. Respiratory complications of obesity. Am Rev Respir Dis 1980; 74:626-629.5. Ray CS, Sue DY, Bray GA, Hansen JE, Wasserman K. Effects of obesity onrespiratory function. Am Rev Respir Dis 1983; 128: 501-506.6. Simeons ATW. The action of chorionic gonadotropin in the obese. Lancer1954; 2: 946-947.7. Simeons ATW. Chorionic gonadotropin in the treatment of obesity. Am JClin Nurr 1964; 15: 188-190.8. Gusman HA. Chorionic gonadotropin in obesity: further clinical observations. Am J Clin Nurr 1969; 22: 686-695.9. Greenway FL, Bray GA. Human chorionic gonadotropin (HCG) in thetreatment of obesity - a critical assessment of the Simeons method. Wesr JMed 1977; 127: 461-463.10. Bray GA, Greenway FL. Pharmacological approaches to treating the obesepatient. Clin Endocrinol Merabol 1976; 5: 455-479.I!. Stewart-Truswell A, Wahlqvist ML. International symposia on nutritionand obesity: the state of the science. MedJ Awr 1985; 142: suppl, S32.12. Stein MR, Julis RE, Peck CC er el. Ineffectiveness of human chorionicgonadotropin in weight reduction - a double-blind srudy. Am J Clin Nurr1976; 29: 940-948.13. Craig LS, Ray RE, Waxier SH, Madigan H. Chorionic gonadotropin in thetreatment of obese women. Am J Clin Nurr 1963; 12: 230-234.14. Katch FI, McArdle WO. Nurririon, Weighr Conrrol and Exercise. 2nd ed.Philadelphia: Lea & Febiger, 1983.15. Hendler RG, Walesky M, Sherwin RS. Sucrose substirution in preventionand reversal of the fall in metabolic rate accompanying hypocaloric diets. AmJ Med 1986; 81: 280-284.16. Bertram SR, Venter I. Obesity and exercise: is weight loss facilitated byexercise? Proceedings of rhe Second Sourh African Sports Medicine AssociarionCongress. Johannesburg: Medical News Group, 1987.17. Frank BW. The use of chorionic gonadotropm hormone in the treatment ofobesity: a double-blind scudy. Am J Clin Nurr 1964; 14: 133-136.

blind, placebo-controlledstudy, the effects of HCG on weight loss were compared with placebo injections. Forty obese women (body mass index 30 kg/m2) were placed on the same diet supplying 5000 kJ per day and received daily intramuscular injections of saline or HCG, 6 days a week for 6 w

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